Phenotypical characterization of children with hypersensitivity reactions to NSAIDs

Abstract

The current ENDA classification does not seem to be adapted for pediatric patients; a modified version does. Our study could help allergists better understand the differences between adults and children in developing hypersensitivity reactions to NSAIDs, but further large-scale prospective longitudinal analyses are required to validate this new classification.

Characteristics of NSAID‐induced hypersensitivity reactions in childhood

“…Mild cutaneous reactions are maculopapular and fixed drug eruptions, and more severe ones are acute generalized exanthematous pustulosis, Stevens‐Johnson syndrome/toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS), which may be even life‐threatening. In one of the largest published series, there was only one pediatric patient belonging to this phenotype, and Guvenir et al. reported one paracetamol/acetaminophen‐induced fixed drug eruption in their study .…”

“…According to ENDA/EAACI/GA 2 LEN recommendations, the five aforementioned phenotypes of NSAID‐H are mainly based on authors’ expertise and published evidence; these studies mainly focus on the adult population (Table ). Subsequent to the publication of these recommendations, several authors focused their studies on the pediatric population, describing similar and divergent phenotypes of NSAID‐H in children …”

“…As an important finding in these studies, the most commonly implicated culprit NSAIDs resulting in confirmed hypersensitivity in young children were ibuprofen, paracetamol and to a lesser extent metamizole, while diclofenac, naproxen, aspirin, and ketoprofen were more common in adolescents . Another objective of more recent studies was to define CI and SR patients and to subsequently highlight possible phenotypes adapted to the pediatric population, based on the EAACI‐ENDA recommendations, by performing an extra‐oral provocation test (OPT) either with aspirin or ibuprofen or with another non‐selective COX‐I inhibitor . Among these confirmed phenotypes, SNIDR is the least frequent one (only one patient in each of the two studies), SNIUAA phenotype was defined in 20%,, or 75% of NSAID hypersensitive children and adolescents, and NIUA, NECD, and NERD phenotypes were defined in 15%‐45%, 7%‐20%, and 3%‐13% of the patients, respectively.…”

“…Another objective of more recent studies was to define CI and SR patients and to subsequently highlight possible phenotypes adapted to the pediatric population, based on the EAACI‐ENDA recommendations, by performing an extra‐oral provocation test (OPT) either with aspirin or ibuprofen or with another non‐selective COX‐I inhibitor . Among these confirmed phenotypes, SNIDR is the least frequent one (only one patient in each of the two studies), SNIUAA phenotype was defined in 20%,, or 75% of NSAID hypersensitive children and adolescents, and NIUA, NECD, and NERD phenotypes were defined in 15%‐45%, 7%‐20%, and 3%‐13% of the patients, respectively. There are also discrepancies reported in adult studies in terms of frequencies of different phenotypes of NSAID‐H, which may appear due to the variations in NSAID consumption or genetic composition .…”

“…NSAID‐induced delayed reactions (SNIDRs) are very rare both in adults and in children (Table ). Mild cutaneous reactions are maculopapular and fixed drug eruptions, and more severe ones are acute generalized exanthematous pustulosis, Stevens‐Johnson syndrome/toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS), which may be even life‐threatening.…”